1. Field of Endeavor
The present invention relates to polymerase chain reactions (PCR), and in particular, to convectively driven PCR thermal-cycling.
2. State of Technology
The polymerase chain reaction (PCR) is widely accepted as the gold standard for identification of biological organisms. PCR is a biochemical method by which the concentration of DNA segments in solution is increased at an exponential rate over time. It is capable of distinguishing between strains of organisms of the same species. PCR typically requires a sample to be repeatedly cycled between temperatures near 95xc2x0 C. and a temperature below 60xc2x0 C.
The primary method of PCR thermal cycling has been to heat and cool some form of chamber containing the PCR sample. Conventional PCR thermal cycling is accomplished by placing the PCR sample in a chamber then heating and cooling the chamber and sample to precise temperature set points. The cycling is repeated until PCR amplification is achieved.
PCT publication WO/9939005 titled: xe2x80x9cRapid Thermocycling for Sample Analysis,xe2x80x9d by the applicant Mayo Foundation for Medical Education and Research, dated Aug. 5, 1999, inventors James, P. Landers, Andreas Huhmer, Robert, P. Oda, and James, R. Craighead provides the following description: xe2x80x9cMethods for performing rapid and accurate thermocycling on a sample are disclosed. Use of non-contact heating and cooling sources allows precise temperature control with sharp transitions from one temperature to another to be achieved. A wide range of temperatures can be accomplished according to these methods. In addition, thermocycling can be performed without substantial temperature gradients occurring in the sample. Apparatus for achieving these methods are also disclosed. A method for pumping a sample through microchannels on a microchip using a non-contact heat source is also disclosed.xe2x80x9d
U.S. Pat. No. 5,942,432 titled: xe2x80x9cApparatus for a Fluid Impingement Thermal Cycler,xe2x80x9d issued Aug. 24, 1999, to Douglas H. Smith, John Shigeura, and Timothy M. Woudenberg, assigned to The Perkin-Elmer Corporation, provides the following description: xe2x80x9cApparatus are disclosed that thermally cycles samples between at least two temperatures. These apparatus operate by impinging fluid jets onto the outer walls of a sample containing region. Because the impinging fluid jets provide a high heat transfer coefficient between the jet and the sample containing region, the sample containing regions are uniformly cycled between the two temperatures. The heat exchange rate between the jets and the sample regions are substantially uniform.xe2x80x9d
U.S. Pat. No. 5,972,667 titled: xe2x80x9cMethod and Apparatus for Activating a Thermo-enzyme Reaction with Electromagnetic Energy,xe2x80x9d issued to Jerome Conia and Claude Larry Keenan, assigned to Cell Robotics, Inc., provides the following description: xe2x80x9cA method and apparatus for activating a thermo-enzyme reaction, such as a polymerase chain reaction or other temperature-sensitive transformation of biological systems are provided. Electromagnetic energy is applied to a target to produce a rapid elevation in the temperature of at least a portion of the target. The electromagnetic energy can be laser energy provided via a laser beam supplied from one or more laser sources. The laser beam can have a wavelength in the infrared range from 750 nm to mm. The source of electromagnetic energy can be used in association with a microscope and/or objective lens to irradiate microscopic targets.xe2x80x9d
U.S. Pat. No. 5,958,349, for a reaction vessel for heat-exchanging chemical processes by Kurt E. Petersen, William A. McMillan, Gregory T. A. Kovacs, and Steven J. Young, patented Sep. 28, 1999 provides the following description: xe2x80x9cA reaction vessel for holding a sample for a heat-exchanging chemical process has two opposing major faces and a plurality of contiguous minor faces joining the major faces to each other. The major and minor faces form an enclosed chamber having a triangular-shaped bottom portion. The ratio of the thermal conductance of the major faces to that of the minor faces is at least 2:1, and the minor faces forming the triangular-shaped bottom portion of the chamber are optically transmissive. The vessel also has a port for introducing a sample into the chamber and a cap for sealing the chamber.xe2x80x9d
U.S. Pat. No. 5,589,136 for a silicon-based sleeve devices for chemical reactions, by Northrup, et al., patented Dec. 31, 1996, provides the following description: xe2x80x9cA silicon-based sleeve type chemical reaction chamber that combines heaters, such as doped polysilicon for heating, and bulk silicon for convection cooling. The reaction chamber combines a critical ratio of silicon and silicon nitride to the volume of material to be heated (e.g., a liquid) in order to provide uniform heating, yet low power requirements. The reaction chamber will also allow the introduction of a secondary tube (e.g., plastic) into the reaction sleeve that contains the reaction mixture thereby alleviating any potential materials incompatibility issues. The reaction chamber may be utilized in any chemical reaction system for synthesis or processing of organic, inorganic, or biochemical reactions, such as the polymerase chain reaction (PCR) and/or other DNA reactions, such as the ligase chain reaction, which are examples of a synthetic, thermal-cycling-based reaction. The reaction chamber may also be used in synthesis instruments, particularly those for DNA amplification and synthesis.xe2x80x9d
The present invention provides a polymerase chain reaction system that heats and cools a fluid through convective pumping. The system includes an upper temperature zone and a lower temperature zone. Channels in the polymerase chain reaction system set up convection cells in the fluid and move the fluid repeatedly through the upper temperature zone and the lower temperature zone creating thermal cycling.
Other features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description and by practice of the invention.